The long-term goal of these studies is to define the intrinsic and extrinsic mechanisms regulating development and function of male gametes. The current aims are to identify genes that: (1) encode proteins likely to have essential roles in the structure or function of spermatogenic cells, (2) have developmentally-regulated expression, (3) transcribe mRNAs unique to spermatogenic cells, and (4) are potentially involved in the effects of environmental agents on spermatogenesis. The hypothesis being tested in current studies is that expression of many genes in spermatogenic cells is regulated by mechanisms intrinsic to these cells, with cell-type specific combinations of transcription factors binding to gene-specific regulatory elements to promote or suppress transcription. We also hypothesize that hormone-dependent extrinsic cues, such as growth factors and other protein signals coming from Sertoli cells, ar necessary to modulate the intrinsic mechanisms regulating gene expression in spermatogenic cells. To carry out these studies, we have cloned and characterized a group of cDNAs unique to spermatogenic cells. Currently being studied by gene expression, transgenic and gene knockout approaches are mRNAs and genes for acrosin (Acr), fibrous sheath component 1 (Fsc- 1), glutathione S-transferase (Gst-s), the IGF-II/cation-independent mannose 6-phosphate receptor (IGF-ii/ci-mpr), and the glycolytic pathway enzymes, glyceraldehyde 3-phosphate dehydrogenase (Gapd-s) and hexokinase (Hk1-s).